Immunology of Infectious Disease News Volume 8.19 | May 20 2020

TOP STORY

Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals

Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2-specific CD8⁺ and CD4⁺ T cells were identified in 70% and 100% of COVID-19 convalescent patients, respectively. [Cell] Abstract | Full Article

(Ranked by impact factor of the journal)

SARS-CoV-2

Identification of Human Single-Domain Antibodies against SARS-CoV-2

Investigators describe the development of a phage-displayed single-domain antibody library by grafting naive complementarity-determining regions into framework regions of a human germline immunoglobulin heavy chain variable region allele. [Cell Host Microbe] Full Article | Graphical Abstracta

Immunogenicity of a DNA Vaccine Candidate for COVID-19

The authors generated a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 spike (S) protein. The engineered construct, INO-4800, resulted in robust expression of the S protein in vitro. [Nat Commun] Full Article

An Inflammatory Profile Correlates with Decreased Frequency of Cytotoxic Cells in COVID-19

Scientists observed a lower perforin⁺ NK cells number in intensive care unit (ICU) compared to non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism. [Clin Infect Dis] Full Article

Cross-Reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections

The authors analyzed plasma from patients infected by SARS-CoV-2 or SARS-CoV, and from infected or immunized mice. Results showed that, while cross-reactivity in antibody binding to the spike protein was common, cross-neutralization of the live viruses may be rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. [Cell Rep] Full Article | Graphical Abstract

Key Residues of the Receptor Binding Motif in the Spike Protein of SARS-CoV-2 That Interact with ACE2 and Neutralizing Antibodies

In vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there were distinct antigenic features in the RBDs of the two viruses. [Cell Mol Immunol] Full Article

TMPRSS2 and TMPRSS4 Promote SARS-CoV-2 Infection of Human Small Intestinal Enterocytes

Researchers report productive infection of SARS-CoV-2 in ACE2⁺ mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. [Sci Immunol] Full Article

The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike

Bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures revealed the high affinity between human dipeptidyl peptidase 4 (DPP4) and the spike receptor-binding domain of SARS-CoV-2. [iScience] Abstract | Full Article | Graphical Abstract

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

T Cell-Inducing Vaccine Durably Prevents Mucosal SHIV Infection Even with Lower Neutralizing Antibody Titers

Researchers immunized macaques with an HIV envelope trimer, either alone to induce neutralizing antibodies (nAbs), or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8⁺ tissue-resident memory T cells. [Nat Med] Full Article

Heterogenous Populations of Tissue-Resident CD8⁺ T Cells Are Generated in Response to Infection and Malignancy

Using single-cell RNA-sequencing and genetic reporter mice, investigators identified discrete lineages of intestinal antigen-specific CD8⁺ T cells, including a Blimp1^hiId3^lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections and a molecularly distinct Blimp1^loId3^hi tissue-resident memory population that subsequently accumulated at later infection time points. [Immunity] Abstract | Graphical Abstract

Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies

The authors investigated the human B cell response in children after natural dengue virus (DENV) infection in the endemic area of Nicaragua and isolated 15 DENV3 type specific monoclonal antibody recognizing the envelope glycoprotein. [Cell Host Microbe] Abstract | Graphical Abstract

Immune-Profiling of ZIKV-Infected Patients Identifies a Distinct Function of Plasmacytoid Dendritic Cells for Immune Cross-Regulation

To characterize immune responses to Zika virus (ZIKV), researchers examined transcriptional signatures of CD4 T, CD8 T, B, and NK cells, monocytes, myeloid dendritic cells, and plasmacytoid dendritic cells from three individuals with ZIKV infection. [Nat Commun] Full Article

Plasma Membrane Damage Causes NLRP3 Activation and Pyroptosis during Mycobacterium tuberculosis Infection

Investigators showed how M. tuberculosis caused caspase-1/NLRP3/gasdermin D-mediated pyroptosis of human monocytes and macrophages. A type VII secretion system mediated, contact-induced plasma membrane damage response occured during phagocytosis of bacteria. [Nat Commun] Full Article

Co-Immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge

Only macaques in the co-administration vaccine group were protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and show 67% risk reduction per exposure. [Cell Rep] Full Article | Graphical Abstract

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Interaction between Microbiota and Immunity in Health and Disease

The authors review features of microbiome-immunity crosstalk and their roles in health and disease, while providing examples of molecular mechanisms orchestrating these interactions in the intestine and extra-intestinal organs. [Cell Res] Full Article

Visit our reviews page to see a complete list of reviews in the immunology of infectious disease research field.

Cidara Therapeutics Doses First Patient in Pivotal Phase III ReSPECT Trial of Rezafungin for Prevention of Invasive Fungal Disease in Patients Undergoing Allogeneic Blood and Marrow Transplantation

Cidara Therapeutics, Inc. Mundipharma announced that the first patient has been dosed in its ReSPECT pivotal Phase III clinical trial evaluating the efficacy and safety of the company’s lead anti-fungal candidate, rezafungin, for the prevention of invasive fungal disease in patients undergoing allogeneic blood and marrow transplantation. [Cidara Therapeutics, Inc.] Press Release

Moderna Announces Positive Interim Phase I Data for Its mRNA Vaccine (mRNA-1273) against Novel Coronavirus

Moderna, Inc. announced positive interim clinical data of mRNA-1273, its vaccine candidate against SARS-CoV-2, from the Phase I study led by the National Institute of Allergy and Infectious Diseases. [Moderna, Inc.] Press Release

Enzo Biochem Launches Proprietary Test for Detection of Coronavirus SARS-CoV-2 IgG Antibody under FDA’s Emergency Use Authorization

Enzo Biochem, Inc. announced that it is currently offering a SARS-CoV-2 IgG ELISA assay kit for serological detection of IgG antibodies against the novel coronavirus under the FDA’s Emergency Use Authorization authority as both products and services. [Enzo Biochem, Inc.] Press Release

US Food and Drug Administration Approves Bristol Myers Squibb’s Pomalyst^® (Pomalidomide) for AIDS-Related and HIV-Negative Kaposi Sarcoma

Bristol Myers Squibb announced that Pomalyst^® was approved by the FDA for patients with AIDS-related Kaposi sarcoma whose disease has become resistant to highly active anti-retroviral therapy, or in patients with Kaposi sarcoma who are HIV-negative. [Bristol Myers Squibb] Press Release

FDA Approves Octapharma USA Investigational New Drug Application for Severe COVID-19 Patients

The FDA has approved the investigational new drug (IND) application submitted by Octapharma USA for a Phase III clinical trial on the efficacy and safety of Octagam^® 10% therapy in COVID-19 patients with severe disease progression. [Octapharma USA, Inc.] Press Release

Coronavirus Vaccine Trials Have Delivered Their First Results – but Their Promise Is Still Unclear

As coronavirus vaccines hurtle through development, scientists are getting their first look at data that hint at how well different vaccines are likely to work. The picture, so far, is murky. [Naure News] Editorial

Open-Access Science Funders Announce Price Transparency Rules for Publishers

Science journals will have to disclose the costs of publishing articles in order for them to be paid for by a coalition of research funders pushing for open access. [ScienceInsider] Editorial

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NEW Postdoctoral Researcher – Pathogenic Fungi (Leibniz Institute for Natural Product Research and Infection Biology)

Postdoctoral Researcher – Peptide-Based Antibiotics (University of Copenhagen)

Postdoctoral Fellow – Innate Lymphocytes and Influenza Pathogeneisi (Oklahoma Medical Research Foundation)

Postdoctroal Fellow – Bacterial Infection (Seattle Children’s Research Institute)

Postdoctoral Researcher – Human Pathogenicity and Fungi (Hans Knöll Institute)

Research Fellow – Infectious Disease (The Lundquist Institute)

Director – Malaria Research (Johns Hopkins University)

Chair – Department of Microbiology and Immunology (Western University)

Group Leader – Anti-Microbial Resistance (Helmholtz Centre for Infection Research)

Research Fellow – COVID-19 Virology (Queen’s University Belfast)

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